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I. Adrenal Cortex and Steroid 21-Hydroxylase Autoantibodies in Adult Patients with Organ-Specific Autoimmune Diseases: Markers of Low Progression to Clinical Addison’s Disease

Chair of Clinical Immunology and Allergy (C.B., M.V., B.P., F.P.), and Chair of Endocrinology (M.B.) from the Institute of Semeiotica Medica; Department of Pediatrics (N.A.G.), University of Padova, Padova; Chair of Immunology (F.T.), Institute of General Pathology, University of Trieste; Department of Laboratory Medicine, Padova General Hospital (M.S.), Padova, Italy; FIRS Laboratories (B.R.S., J.F., S.C.), RSR Ltd, Parc Ty Glas, Llanishen, Cardiff CF4 5DU and Department of Medicine, University of Wales, College of Medicine, Heath Park, Cardiff CF4 4XN, United Kingdom

Address all correspondence and requests for reprints to: Professor Corrado Betterle, Istituto di Semeiotica Medica, Cattedra di Immunologia Clinica e Allergologia, Università di Padova, Via Ospedale 105, 35128 - Padova, Italy.

Adrenal cortex antibodies (ACA) were measured by immunofluorescence in 8840 adult patients with organ-specific autoimmune diseases without overt hypoadrenalism. Sixty-seven (0.8%) patients were ACA-positive, with the highest prevalence in those with premature ovarian failure (8.9%). Forty-eight ACA-positive and 20 ACA-negative individuals were enrolled into a prospective study. Antibodies to steroid 21-hydroxylase (21-OH), steroid 17-hydroxylase (17-OH) and cytochrome P450 side chain cleavage enzyme (P450scc) were measured by immunoprecipitation assay. Human leucocyte antigens D-related (HLA-DR) genotyping was also carried out and adrenal function assessed by ACTH test. On enrollment, 75% of ACA-positive patients had a normal adrenal function, while 25% revealed a subclinical hypoadrenalism. 21-OH antibodies were positive in 91% of ACA-positive sera. Eleven patients were positive for steroid-cell antibodies by immunofluorescence, and 9 revealed a positivity for antibodies to 17-OH and/or P450scc. During the prospective study, overt Addison’s disease developed in 21% and subclinical hypoadrenalism in 29% of ACA-positive patients, while 50% maintained normal adrenal function. Progression to Addison’s disease was more frequent in patients with subclinical hypoadrenalism, high titers of ACA and higher levels of 21-OH antibodies, complement-fixing ACA and HLA-DR3 status. All 20 persistently ACA-negative patients were also negative for antibodies to 21-OH, 17-OH, and P450scc, and all maintained normal adrenal function during follow-up. In conclusion, the detection of ACA/21-OH antibodies in adults is a marker of low progression toward clinical Addison’s disease. .

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